FK506-binding protein 51 (FKBP51) is an immunophilin with isomerase activity, which performs important biological functions in the cell. It has recently been involved in the apoptosis resistance of malignant melanoma. The aim of this study was to investigate the possible role of FKBP51 in the control of response to ionizing radiation (Rx) in malignant melanoma. FKBP51-silenced cells showed reduced clonogenic potential after irradiation compared with non-silenced cells. After Rx, we observed apoptosis in FKBP51-silenced cells and autophagy in non-silenced cells. The FKBP51-controlled radioresistance mechanism involves NF-jB. FKBP51 was required for the activation of Rx-induced NF-jB, which in turn inhibited apoptosis by stimulating X-linked inhibitor of apoptosis protein and promoting authophagy-mediated Bax degradation. Using a tumor-xenograft mouse model, the in vivo pretreatment of tumors with FKBP51-siRNA provoked massive apoptosis after irradiation. Immunohistochemical analysis of 10 normal skin samples and 80 malignant cutaneous melanomas showed that FKBP51 is a marker of melanocyte malignancy, correlating with vertical growth phase and lesion thickness. Finally, we provide evidence that FKBP51 targeting radiosensitizes cancer stem/initiating cells. In conclusion, our study identifies a possible molecular target for radiosensitizing therapeutic strategies against malignant melanoma.

No abstract

Survivin is a recently described apoptosis inhibitor selectively over-expressed in most tumors. Immunohistochemistry was used to investigate a potential role of survivin as an early predictor of malignant transformation in precancerous and cancerous lesions of the oral cavity. Survivin was present in 10/30 cases (33%) of oral precancerous lesions without malignant progression, and in 15/16 cases (94%) of oral precancerous lesions evolved into full-blown squamous cell carcinoma. Tumors that progressed from these precancerous lesions retained widespread survivin positivity (100%). Variations among group means were highly statistically significant (p < 0.001). No significant correlation was found between survivin expression and the degree of dysplasia. High expression of cytoplasmic/nuclear survivin is an early event during oral carcinogenesis and may provide a useful tool for the identification of precancerous lesions at higher risk of progression into invasive carcinoma.

Low E-Cadherin expression is a negative prognostic factor of OSCC and is likely due to the hypermethylation of CDH1 promoter. The delocalization of E-cadherin from membrane to cytoplasm could be also due to the increased expression of EGFR in OSCC and the consequent increase of E-cadherin co-internalization with EGFR.

No abstract

No abstract

The results of this multicenter study showed that there is a noticeable difference in the expression of PCNA, p53, cyclin-D1, and AgNOR in tissues from patients with LLSCC and controls.

ABSTRACT.Purpose: To determine the efficacy of echography with new generation contrast agents in visualizing vascularization of choroidal malignant melanomas. Methods: An echographic contrast medium consisting of phospholipidic microbubbles filled with sulphur hexafluoride (Sonovue 1 ) was used to visualize microcirculation in 25 cases of choroidal lesions already diagnosed with standardized echography (21 choroidal malignant melanomas, four disciform lesions). Results: In untreated malignant melanomas contrast agent echography revealed the presence of a dense microcirculation inside the mass. In one case vitreal seeding of the contrast agent was detectable before enucleation and histological examination revealed the presence of tumoral cells. In 12 cases treated with transpupillary thermotherapy, contrast agent echographic evaluation showed heavy regression of microcirculation after 1 week, confirmed in one case by histology, and a reduction of 70-80% in dimensions after 6 months (which appeared to have stabilized at subsequent examinations). In four cases treated with proton beam brachytherapy 2 years prior to our examination, contrast agent echography showed the absence of a microvascular network and the presence of large vessels and blood lakes. In four cases of disciform lesion, deep and superficial retina-associated vascularization was observed, with a weak spread of contrast agent inside the lesion. Conclusion: Live representation with good resolution of choroidal malignant melanoma microcirculation was obtained.